Development and evaluation of a new luciferase immunosorbent assay to detect GII.6 norovirus-specific IgG in different domestic and wild animals.

Noroviruses (NoVs) are the leading viral pathogens globally causing acute gastroenteritis (AGE) in humans, posing a significant global health threat and economic burden. Recent investigations revealed that human NoVs had been detected in different animals, which raises concerns about whether NoVs are potential zoonotic diseases. This study developed a novel luciferase immunosorbent assay (LISA) to detect GII.6 NoV IgG based on P protein of VP1. The LISA showed high specificity (99.20%) and sensitivity (92.00%) with 4-16 times more sensitivity compared with an ELISA. NoV-LISA was reproducible with human serum regarding the inter- and intra-assay coefficient of variance values. Potential cross-reactivity was also evaluated using mice serum immunized by other antigens, which showed that NoV-LISA could differentiate GII.6 NoV from rotavirus and various genotypes of NoV. Specific GII.6 NoV IgG was widely detected in different domestic and wild animals, including dogs, pigs, bats, rats, and home shrews, with various IgG-positive rates ranging from 2.5 to 74.4%. In conclusion, our newly developed NoV-LISA assay is suitable for NoV-specific IgG detection in humans and animals. The wide distribution of IgG antibodies against human NoV indicates potential zoonotic transmission between humans and animals.

Pilot drug and therapeutic committee programme in Sierra Leone: A descriptive mixed method study.

AIMS: Irrational medicine use is a global crisis, but incidences are proportionately higher in low- and middle-income countries such as Sierra Leone. This study explores the structure, functions and challenges of drug and therapeutics committees (DTCs), an intervention towards irrational medicine use recently piloted in Sierra Leone. METHODS: A 2-phase mixed-method study design was used in this study. Firstly, a cross-sectional survey was conducted on all pharmacists who have worked for at least 1 year in DTC-piloted hospitals, using an online questionnaire to assess DTCs' structure, indicators and challenges. In phase 2, all eligible pharmacists were invited for a semistructured online interview using the WhatsApp messaging application to get deeper insights into the key issues that emerged from the survey; however, only 5 of the 7 consented to participate. MS Excel 2019 and NVivo version 12 were respectively used for data management and analysis. RESULTS: A total of 6 survey responses and 5 interviews were included in the analysis. Participants are pharmacists from the 7 hospitals in Sierra Leone where DTC was piloted. Most DTCs are comprised of a minimum of 10 members consisting of both medical and hospital administrative staff. The main functions of DTCs are ensuring rational medicines use, monitoring and reporting adverse drug reactions. All 7 hospitals with established pilot DTCs have different subcommittees operating at varying functionality levels, ranging from effective to nonfunctional. The main challenges in DTC functions and maintenance are funding (n = 6), DTC decision implementation (n = 4), and unmotivated members (n = 4). Strategies suggested to improve DTCs at public hospitals and nationwide include resource allocation, monitoring and evaluating DTC functions and its members' capacity building. CONCLUSION: DTCs present a compelling opportunity towards achieving rational medicines use at the hospital level in Sierra Leone. Nonetheless, the lack of funding and operational resources are significant limitations that must be noted by policymakers before expanding DTC programmes to other hospitals in Sierra Leone.

Serological surveillance of GI norovirus reveals persistence of blockade antibody in a Jidong community-based prospective cohort, 2014-2018.

Introduction: Herd immunity against norovirus (NoV) is poorly understood in terms of its serological properties and vaccine designs. The precise neutralizing serological features of genotype I (GI) NoV have not been studied. Methods: To expand insights on vaccine design and herd immunity of NoVs, seroprevalence and seroincidence of NoV genotypes GI.2, GI.3, and GI.9 were determined using blockade antibodies based on a 5-year longitudinal serosurveillance among 449 residents in Jidong community. Results: Correlation between human histo-blood group antigens (HBGAs) and GI NoV, and dynamic and persistency of antibodies were also analyzed. Seroprevalence of GI.2, GI.3, and GI.9 NoV were 15.1%-18.0%, 35.0%-38.8%, and 17.6%-22.0%; seroincidences were 10.0, 21.0, and 11.0 per 100.0 person-year from 2014 to 2018, respectively. Blockade antibodies positive to GI.2 and GI.3 NoV were significantly associated with HBGA phenotypes, including blood types A, B (excluding GI.3), and O+; Lewis phenotypes Leb+/Ley+ and Lea+b+/Lex+y+; and secretors. The overall decay rate of anti-GI.2 antibody was -5.9%/year (95% CI: -7.1% to -4.8%/year), which was significantly faster than that of GI.3 [-3.6%/year (95% CI: -4.6% to -2.6%/year)] and GI.9 strains [-4.0%/year (95% CI: -4.7% to -3.3%/year)]. The duration of anti-GI.2, GI.3, and GI.9 NoV antibodies estimated by generalized linear model (GLM) was approximately 2.3, 4.2, and 4.8 years, respectively. Discussion: In conclusion, enhanced community surveillance of GI NoV is needed, and even one-shot vaccine may provide coast-efficient health benefits against GI NoV infection.

Under-five mortality in Sierra Leone and possible associated factors: evidence from the 2019 Demographic and Health Survey.

High under-five mortality rate remains one of the public health challenges, especially in Sub-Saharan Africa, accounting for more than half of all global cases. Sierra Leone was and is still one of the countries with the highest under-five mortality rate. Using the latest 2019 Sierra Leone Demographic and Health Survey data, we investigated factors associated with under-five mortality in Sierra Leone. A total of 9771 mothers aged 15-49 years in the country were interviewed and included in the analysis. The dependent variable is child status (dead = 1; alive = 0). A total of 871 (9%) children died before their fifth birthday. The maternal age of 20-24 years [adjusted odds ratios (AOR) = 0.46; 95% confidence interval (CI) = 0.33-0.64; P < 0.001] up to 40-44 years (AOR = 0.43; CI = 0.27-0.7; P = 0.001), currently breastfeeding (AOR = 0.20; CI = 0.17-0.24; P < 0.001), maternal media exposure and usage of reading newspapers/magazines less than once a week (AOR = 0.48; CI = 0.28-0.85; P = 0.011) were more likely to enhance child survivability through their fifth birthday. Also, the child sex being female (AOR = 0.68; CI = 0.59-0.79) was more likely to survive under-five mortality compared to their male counterpart. On the other hand, mothers who listened to radio at least once a week (AOR = 1.31; CI = 1.08-1.59; P = 0.007) watched television less than once a week (AOR = 1.48; CI = 1.16-1.90), had two (AOR = 3.4, CI = 2.78-4.16; P < 0.001) or three and above birth (AOR = 8.11; CI = 6.07-10.83; P < 0.001) in five years, had multiple birth children (AOR = 1.41; CI = 1.08-1.86) and very small-sized child at birth (AOR= 1.95; CI = 1.41-2.70) were more likely to lose their children below the age of 5 years. The factors contributing to under-five mortality in Sierra Leone are critical to ensuring child survival and improving maternal health. Breastfeeding, maternal age, media exposure, child's sex, multiple birth type, very small-sized child and the total number of births in 5 years were significant drivers of under-five mortality. The result affirms the need for attention to be focused on enhancing the survival rate of under-five children in Sierra Leone.

Serological surveillance of noroviruses in a community-based prospective cohort: a study protocol.

INTRODUCTION: Noroviruses are the leading cause of viral acute gastroenteritis affecting all age groups. Since 2014, the previous rarely reported GII.P17-GII.17 and recombinant GII.P16-GII.2 norovirus emerged, replacing GII.4 predominant genotype, causing increased outbreaks in China and other countries. Meanwhile, GII.4/2012 Sydney strain has re-emerged as the dominant variant in many places in 2015-2018. The role of herd immunity as the driving force during these new emerging or re-emerging noroviruses is poorly defined. Serological surveillance studies on community-based prospective cohort on norovirus are highly needed. METHODS AND ANALYSES: This study will include 1000 out of 9798 participants aged 18 years and above from Caofeidian district, Tangshan city, northern China. Baseline data on sociodemographic characteristics and blood samples were collected in 2013-2014. Blood collection will be replicated annually throughout the cohort until 2023. Saliva samples were also collected in 2016. The seroprevalence and seroincidence of blockade antibodies against norovirus genotypes of GII.P17-GII.17, GII.P16-GII.2, the re-emerged GII.4/2012 and potential novel pandemic variants will be evaluated by ELISA. Associations between genotype blockade antibodies and sociodemographic factors and human histo-blood group antigens will be evaluated using univariate and multivariate analysis. The dynamics of herd immunity duration will be estimated in this longitudinal surveillance. ETHICS AND DISSEMINATION: The study has been approved by the Ethical Committees of the Staff Hospital of Jidong oil-field of China National Petroleum Corporation. This study will provide insight into the seroprevalence and seroincidence of noroviruses, and their relationships with sociodemographic characteristics and genetic susceptibility. It will also explain herd immunity of the emerged and re-emerged genotypes or variants. The study will further enable an understanding of the mechanism driving the replacement of norovirus genotypes. Research findings will be disseminated in peer-reviewed journals and at scientific meetings.

Characterization of Antigenic Relatedness Among GI Norovirus Genotypes Using Serum Samples From Norovirus-Infected Patients and Mouse Sera.

Characterizing diversity and the antigenic relatedness of norovirus remains a primary focus in understanding its biological properties and vaccine designs. The precise antigenic and serological features of GI genotypes have not been studied. The study represented an investigation on a gastroenteritis outbreak related to GI.3 norovirus and the three most detected GI genotypes, GI.2 (belonging to immunotype B), GI.3 and GI.9 (belonging to immunotype C), were selected to characterize their phylogenetic relationship, HBGA binding profiles and antigenic relatedness within (intra-immunotype), and between (inter-immunotypes) genotypes using mouse sera and patient's serum samples from the GI.3 related outbreak. Wide HBGA binding profiles and evolution of binding affinity were observed in the three GI genotypes studied. A low specific blockade antibody to GI.3 in the population generated the pool of susceptible individuals and supported virus spread in the outbreak. We found strong blockade immune response in homologous strains, moderate intra-immunotype blockade but weak inter-immunotypes blockade in humans following GI.3 norovirus infections. These findings further support the immunotypes grouping and will be valuable for optimizing the design of norovirus vaccine.